ReviewPregnancy and liver disease
Section snippets
Summary
Pregnancy associated liver diseases affect up to 3% of pregnant women and are the most frequent cause of liver dysfunction in pregnancy. When severe, they are associated with significant morbidity and mortality for both mother and infant [1], [2], [3]. A rapid evaluation to distinguish them from non-pregnancy related liver dysfunction is essential, in order to facilitate appropriate management. Liver disease unrelated to pregnancy can present de novo in pregnancy, or pregnancy can occur in
Normal physiological changes in pregnancy
In a normal pregnancy many physiological and hormonal changes occur within the human body, some of which can mimic those seen in women with liver disease. There is a rise in maternal heart rate, cardiac output increases by 40%, the circulating plasma volume increases by 30% and there is a reduction in peripheral vascular resistance. These physiological changes result in a hyper-dynamic circulation; a physiological state that is common in patients with decompensated chronic liver disease.
Pregnancy related liver diseases
The liver diseases specific to the pregnant state can be classified into those of early pregnancy (hyperemesis gravidarum (HG)) and those of late pregnancy (acute fatty liver of pregnancy (AFLP), pre-eclampsia with hepatic involvement including haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome, liver rupture/infarction and intrahepatic cholestasis of pregnancy (ICP)). The typical pattern of abnormal serum liver tests in specific gestational liver diseases are given in Table 3
Hyperemesis gravidarum
HG is the most severe form of illness within the spectrum of nausea and vomiting of pregnancy. It is defined as intractable vomiting, resulting in dehydration, ketosis and weight loss of greater than 5%. It complicates between 0.3% and 2% of pregnancies and symptoms usually but not exclusively begin before 9 weeks gestation [6], [7]. The exact aetiology of HG is unclear. Human chorionic gonadotropin (HCG) hormone, which peaks in the first trimester has been shown to correlate with the severity
Intrahepatic cholestasis of pregnancy
Intrahepatic cholestasis of pregnancy (ICP) is the commonest pregnancy-specific liver disease. It is a reversible form of cholestasis characterized by pruritus in pregnancy and elevated fasting or post-prandial serum bile acids with spontaneous relief of signs and symptoms within 6 weeks of delivery [20]. ICP has a high recurrence rate in subsequent pregnancies. It has a variable incidence, ranging from 3–5% of pregnant women in Chile, to 0.7% in the UK; it is rarely reported in African
Pre-eclampsia, eclampsia and haemolysis, elevated liver enzymes, low platelets (HELLP) syndrome
Pre-eclampsia is a multisystem disorder defined by the international society for the study of hypertension in pregnancy as de novo hypertension after the 20th week of pregnancy (blood pressure (BP) 140/90) combined with proteinuria (>300 mg/day), other maternal organ dysfunction, such as renal insufficiency, liver involvement, neurological or haematological complications, uteroplacental dysfunction, or fetal growth restriction [47]. In a patient with pre-existing essential hypertension,
Hepatic rupture, infarction and haematoma
Hepatic haemorrhage and rupture can complicate pre-eclampsia, eclampsia, HELLP syndrome and patients with AFLP and is associated with a 50% mortality [63]. Patients can present with abdominal pain, pyrexia and, if severe, hypovolaemic shock and cardiovascular collapse. Laboratory investigations reveal transaminases in the several thousands, leucocytosis and anaemia. Imaging in the form of computed tomography or magnetic resonance is the investigation of choice [64]. Contained haematomas can be
Acute fatty liver of pregnancy
AFLP is a medical and obstetric emergency as it can be fatal for both the mother and baby without early recognition and appropriate management [69], [70]. It is a rare complication of pregnancy, usually occurring in the third trimester, and in the UK affects approximately 1 in 20,000 pregnancies [71], with the true incidence likely however to be higher with underreporting of subclinical/milder forms. Risk factors include nulliparity, male infants and twin pregnancies.
The presentation is similar
Cirrhosis and portal hypertension
In women with cirrhosis, fertility is reduced and pregnancy is rare secondary to metabolic and endocrine dysfunction [1], [81], [82], [83], [84], [85], [86]. Disruption of the hypothalamic-pituitary axis in conjunction with disturbed oestrogen metabolism leads to anovulation, amenorrhoea and infertility [84], [85]. When pregnancy does occur there is an increased rate of spontaneous pregnancy loss, preterm labour and perinatal death [87]. For the mother there is a risk of worsening liver
Acute viral infections and pregnancy
Acute viral hepatitis is the commonest cause of jaundice occurring in pregnancy worldwide [150]. Hepatitis A virus infection in pregnancy has a clinical course similar to the non-pregnant population and fulminant hepatitis is rare [151]. Although hepatitis A virus infection in pregnancy is not a major cause of maternal or neonatal morbidity, in utero infection has been associated with fetal meconium peritonitis, neonatal cholestasis and preterm labour [152], [153], [154]. It is therefore
Conclusion
Liver disease in pregnancy and pregnancy in women with liver disease is rare. However, this is a clinically important group of patients due to the increased morbidity and mortality for both the mother and baby. The spectrum of disease and presentation varies hugely, resulting in delays in diagnosis and appropriate management. The disorders are complex and patients benefit from multi-disciplinary input by experienced physicians in specialist centres. It is important to ensure that women of
Conflict of interest
The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.
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